Surgery-Free Alternative Is Favorably Accepted Among Women at Risk of Ovarian Cancer

The majority of women at a high risk of developing ovarian cancer reported having a favorable attitude toward adopting a two-step risk-reducing early salpingectomy and delayed oophorectomy (RRESDO) instead of a risk-reducing salpingo-oophorectomy (RRSO), according to findings from a multicenter, questionnaire-study published in the British Journal of Obstetrics and Gynaecology.¹

Among 683 participants, 69.1% of premenopausal women who had not undergone RRSO (n = 262) said they found it acceptable to participate in a research study offering RRESDO, a two-stage surgical alternative to RRSO. Moreover, premenopausal women who were also concerned about potential risk of sexual dysfunction were more likely to find RRESDO to be an acceptable alternative (odds ratio (OR) = 2.9; 95% CI, 1.2-7.7; P = .025).

In retrospect, women who underwent RRSO (n = 346) who are experiencing sexual dysfunction following their surgery were more likely to find RRESDO acceptable (OR = 5.3; 95% CI, 1.2-27.5; P <.031).

According to the study, women who are at a high risk of developing ovarian cancer are typically offered standard RRSO, which has been shown to be an effective method of ovarian cancer prevention. However, the surgery is associated with significant risk of complications, as well as the potential for early menopause in premenopausal women. Early menopause has been linked to an increased risk of heart disease, osteoporosis, vasomotor symptoms, neurocognitive decline, and sexual dysfunction. With these statistics, many women elect to delay RRDO until after menopause, which means they live as high-risk individuals for potentially a prolonged period of time.

“While hormone replacement therapy (HRT) has been shown to mitigate some symptoms [of early menopause], it does not appear to alleviate sexual dysfunction or increase satisfaction levels following standard preventive surgery involving removal of ovaries,” said lead study author Faiza Gaba, MBBS, MRCOG, of the Wolfson Institute of Preventive Medicine at Queen Mary University of London in a press release.² “However, HRT-use in breast cancer unaffected women undergoing premenopausal removal of their ovaries is essential to reduce the risk of heart disease, osteoporosis and neurocognitive decline. The new two-step surgery offers further options to women considering surgical prevention.”

Eligible participants had to be women aged 18 years or older from the United Kingdom who were at an increased risk of developing ovarian cancer due to pathogenic variants in an ovarian cancer gene such as BRCA1, BRCA2, RAD51C, RAD51D, or BRIP1, or a strong family history of ovarian cancer or breast cancer and ovarian cancer. Strong family history was defined as having 2 or more first-degree relatives with ovarian cancer in BRCA1/2–negative or untested women.

Non–United Kingdom residents or women with a personal history of ovarian cancer were not eligible for enrollment.

Participants provided a written consent and were given the option to complete the questionnaire via paper or web. The questionnaire consisted of 39 questions regarding socio-demographic information, surgical/menstrual/family history, and whether potential health consequences of early menopause influences their decision to undergo, delay, or decline RRSO.

Additionally, participants were instructed to answer different sections depending on if they had previously undergone RRSO. Topics covered for women who had not undergone RRSO included the benefits and limitations of undergoing RRESDO, acceptability of undergoing RRESDO or participating in an RRESDO-offering clinical study, and anticipated timing of future surgical intervention. Participants who had already undergone RRSO answered questions regarding retrospective acceptability of RRESDO had it been offered. Additional questions were asked regarding whether patients used HRT, menopause sequelae following RRSO, and satisfaction and regret following RRSO.

Regarding participant characteristics, women who had not undergone RRSO (n = 337) were significantly younger (median, 38.25 years) compared with women who had (n = 346; median 51.53 years; P <.001). The mean parity was 1.92 among the no RSSO cohort versus 2.18 in the RRSO cohort (P <.001). Nulliparous was 64.6% and 83.4%, respectively.

Additionally, 78.2% of participants in the non-RRSO cohort were premenopausal while 66.1% of participants in the other cohort were premenopausal at the time of the procedure (P = .001).

Among participants in the non-RRSO cohort, 46.6% were BRCA1 carriers, 50.7% were BRCA2 carriers, and 1.5% were BRCA1 and BRCA2 carriers. Among participants who had already undergone RRDO, these percentages were 46.8%, 46.5%, and 2%, respectively. These individuals were all considered at high risk of developing ovarian cancer.

Participants in the non-RSSO and RSSO cohorts who were considered intermediate risk were RAD51C carriers (0% vs 0.3%, respectively), BRIP1 carriers (0.9% vs 0.3%), BRCA1/BRCA2-negative individuals with a strong family history of ovarian cancer (0.3% vs 0.9%), and BRCA1/2 untested with strong family history of disease (0.6% vs 0.9%), those unsure of their genetic test results (1.2% vs 1.7%), those with a personal history of breast cancer (22.8% vs 46.2%), those with a personal history of other cancers (1.8% vs 2.6%), individuals who had undergone a therapeutic mastectomy (20.8% vs 41.3%), those who received breast surgery for benign breast pathology (0% vs 1.2%), and those who underwent cosmetic breast surgery (0.6% vs 0.3%).

About 90% of all participants were Caucasian.

Regarding the questionnaire among premenopausal women who had not undergone RRSO, 36.26% and 32.82% answered probably and maybe, respectively, when asked whether they would participate in a research study offering RRESDO.

Among participants, factors that affected acceptability of undergoing/retrospective acceptance RRESDO included prior knowledge of tubal origin of ovarian cancer, personal history of breast cancer, previous risk-reducing mastectomy, family complete, carrier status, martial status, ethnicity, education, income, timing of future ovarian cancer prevention surgery, family history, concerns over premature menopause sequelae (hot flushes/night sweats, looking older, decreased libido/other sexual side effects, loss of fertility, osteoporosis, heart disease, dementia/memory dysfunction, impact on survival, and acceptability of having to take HRT until 51 years old).

With these findings, the multicenter PROTECTOR (Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal) trial is ongoing evaluating premenopausal women who are at an increased risk of developing ovarian cancer due to genetic mutation or strong family history of ovarian/ovarian and breast cancer.³ Participants in the PROTECTOR study are able to self-select between 3 arms: RRSO, RRESDO, and control/no surgery. The primary goal of the study is to determine the impact RRESDO has on sexual function.

“The new two-step operation offers additional options for women (who may have not undergone surgical prevention) to reduce their ovarian cancer risk while avoiding the negative impact of early menopause,” researcher Ranjit Manchanda, MBBS, PhD, MRCOG, also of Wolfson Institute of Preventive Medicine, concluded in a press release. “Our study shows a large proportion of eligible women wish to consider this. UK women who wish to do so now have the option of joining the PROTECTOR study.”

References

1. Gaba F, Blyuss O, Chandrasekaran D, et al. Attitudes towards risk‐reducing early salpingectomy with delayed oophorectomy for ovarian cancer prevention: a cohort study. Published ahead of print, August 16, 2020. BJOG. doi:10.1111/1471-0528.16424
2. New surgical approach for women at risk of ovarian cancer. Queen Mary University of London. News release. Published August 23, 2020. Accessed August 25, 2020. https://bit.ly/2YwuHlG.
3. Protector study. 2020. Accessed August 25, 2020. https://bit.ly/3grbnwg.